X chromosome inactivation and active X upregulation in therian mammals: facts, questions, and hypotheses

Veitia, Reiner A.; Veyrunes, Frédéric; Bottani, Samuel; Birchler, James A.

doi:10.1093/jmcb/mjv001

Cited by 48 publications

(36 citation statements)

References 95 publications

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“…But the fact that ploidy-specific expression regulation of these genes did not evolve suggests that even for these dosage-sensitive genes, dosage imbalance is apparently tolerated (in haploids). Taken together, our results argue against Ohno's hypothesis for both haploid and diploid cells and demonstrate that, at least in humans, precise gene regulation for dosage balance, even for members of large protein complexes, are much less critical than is commonly thought (Veitia et al 2015). In the future, it would be interesting to generate proteomic data from human haploid cells to allow validating the above findings at the proteomic level, as was recently done in human diploid cells (Chen and Zhang 2015).…”

supporting

confidence: 55%

The X to Autosome Expression Ratio in Haploid and Diploid Human Embryonic Stem Cells

Chen

Zhang

2016

Mol Biol Evol

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Ohno proposed that the expression levels of X-linked genes have been doubled to compensate the degeneration of Ylinked homologs during the evolution of mammalian sex chromosomes, but RNA sequencing in human somatic tissues showed no such upregulation for the vast majority of X-linked genes. Here we report that the X to autosome expression ratio equals $1 in haploid human parthenogenetic embryonic stem (pES) cells and $0.5 in diploidized pES cells, both with one active X chromosome. Although we confirmed the upregulation of $5% of X-linked genes encoding members of large protein complexes in diploids, these genes are also upregulated in haploids, breaking the otherwise balanced dosage. These findings argue against Ohno's hypothesis for both haploid and diploid cells and demonstrate that, at least in humans, precise gene regulation for dosage balance, even for members of large protein complexes, is much less critical than is commonly thought.

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supporting

confidence: 55%

The X to Autosome Expression Ratio in Haploid and Diploid Human Embryonic Stem Cells

Chen

Zhang

2016

Mol Biol Evol

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“…The apparent increase in female mortality occurs despite gene expression by two X chromosomes (although most loci on one or the other X chromosome are not expressed in a given cell). The expression of deleterious mutations is thought to be masked when the two X chromosomes have equal inactivation probabilities (96). Sex differences in gene expression are known later in pregnancy and later in life (97-99), but we lack information on how sex differences in gene expression earlier in pregnancy might contribute to female-biased mortality.…”

Section: Discussionmentioning

confidence: 99%

The human sex ratio from conception to birth

Orzack

Stubblefield

Akmaev³

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

235

170

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We describe the trajectory of the human sex ratio from conception to birth by analyzing data from (i) 3-to 6-d-old embryos, (ii) induced abortions, (iii) chorionic villus sampling, (iv) amniocentesis, and (v) fetal deaths and live births. Our dataset is the most comprehensive and largest ever assembled to estimate the sex ratio at conception and the sex ratio trajectory and is the first, to our knowledge, to include all of these types of data. Our estimate of the sex ratio at conception is 0.5 (proportion male), which contradicts the common claim that the sex ratio at conception is malebiased. The sex ratio among abnormal embryos is male-biased, and the sex ratio among normal embryos is female-biased. These biases are associated with the abnormal/normal state of the sex chromosomes and of chromosomes 15 and 17. The sex ratio may decrease in the first week or so after conception (due to excess male mortality); it then increases for at least 10-15 wk (due to excess female mortality), levels off after ∼20 wk, and declines slowly from 28 to 35 wk (due to excess male mortality). Total female mortality during pregnancy exceeds total male mortality. The unbiased sex ratio at conception, the increase in the sex ratio during the first trimester, and total mortality during pregnancy being greater for females are fundamental insights into early human development.he sex ratio at conception in humans is unknown, despite hundreds of years of speculation and research. Investigations of the sex ratio date back at least as far as Graunt (1) who described a net excess of male births (2). By the late 1800s, it was clear that more males than females die during later pregnancy (3). Beyond these facts, the demographic and genetic dynamics of the sex ratio from conception to birth are poorly resolved.The claim that the conception or primary sex ratio (PSR) is more male-biased than the birth sex ratio appears often in textbooks (4, 5) and in the scientific literature (e.g., refs. 6-11), usually with little or no description of evidence. Estimates of the PSR in these studies are typically 0.56 (proportion males) or greater. Many fewer researchers have claimed that the PSR is unbiased or slightly male-biased (12-16). A handful of researchers has claimed or implied that the PSR is female-biased (17-19) or claimed that the PSR cannot be estimated due to lack of appropriate data and/or methodological problems (20)(21)(22).Previous estimates of the PSR have no meaningful basis in data from the time of conception (or within at least a month of it). At best, the PSR has been estimated via backward extrapolation from data on induced or spontaneous abortions, fetal deaths, or live births; most of the non-live-birth data stems from the second or third trimester of pregnancy. In addition, even if one ignores the fallibility of extrapolation, biased estimates of the PSR based on spontaneous abortions and fetal deaths have usually been regarded as arising from unbiased samples of a population of embryos or fetuses having a biased PSR. The alternativ...

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“…This is achieved by X inactivation in mammals, or X repression in Caenorhabditis elegans . These repressive systems have been extensively reviewed [9, 75]. Here, we will limit our discussion to the balance in the heterogametic sex.…”

Section: Dosage Compensation Between Sex Chromosomes and Autosomesmentioning

confidence: 99%

Dosage compensation of the sex chromosomes and autosomes

Distèche

2016

Seminars in Cell & Developmental Biology

112

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Males are XY and females are XX in most mammalian species. Other species such as birds have a different sex chromosome make-up: ZZ in males and ZW in females. In both types of organisms one of the sex chromosomes, Y or W, has degenerated due to lack of recombination with its respective homolog X or Z. Since autosomes are present in two copies in diploid organisms the heterogametic sex has become a natural "aneuploid" with haploinsufficiency for X- or Z-linked genes. Specific mechanisms have evolved to restore a balance between critical gene products throughout the genome and between males and females. Some of these mechanisms were co-opted from and/or added to compensatory processes that alleviate autosomal aneuploidy. Surprisingly, several modes of dosage compensation have evolved. In this review we will consider the evidence for dosage compensation and the molecular mechanisms implicated.

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X chromosome inactivation and active X upregulation in therian mammals: facts, questions, and hypotheses

Cited by 48 publications

References 95 publications

The X to Autosome Expression Ratio in Haploid and Diploid Human Embryonic Stem Cells

The X to Autosome Expression Ratio in Haploid and Diploid Human Embryonic Stem Cells

The human sex ratio from conception to birth

Dosage compensation of the sex chromosomes and autosomes

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